title: Efficacy of rapamycin in scleroderma: a case study.
abstract: Scleroderma is a common autoimmune disorder with no effective therapy. Current concepts of scleroderma include the hypothesis that scleroderma results from excess conversion of endothelial cells to fibroblast like cells, called endothelial mesenchymal transformation. This process is thought to be mediated by cytokines including transforming growth factor beta (TGFb), which causes increased collagen synthesis, resulting in fibrosis, the hallmark of the disease. In vitro studies have hypothesized that rapamycin may be of benefit in scleroderma due to antagonism of collagen synthesis. Given that rapamycin has antiangiogenic activities, inhibits wound healing, and prevents the synthesis of collagen in vivo, we tried rapamycin in a patient with scleroderma. We observed rapid improvement in skin stiffness and mobility. Our results provide the rationale for larger clinical trials of rapamycin in scleroderma and other fibrotic disorders.
authors.affiliation: Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Levi
authors.initials: L
authors.lastname: Fried
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kirsner
authors.forename: Sulochana
authors.initials: S
authors.lastname: Bhandarkar
authors.forename: Jack L
authors.initials: JL
authors.lastname: Arbiser
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008648:Mesoderm / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications; D012595:Scleroderma, Systemic / Q000188:drug therapy*; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D003094:Collagen; D020123:Sirolimus